DISCUSSION(4)

Implantation occurs on the antimesometrial side of the uterus during early pregnancy. The decidualization of stroma cells begins on the antimesometrial side and later spreads to the mesometrial side. The greater expression of CRBP, CRABP, and CRABP II on the mesometrial side at Day 1 suggests that the retinoic acid signal is involved in establishing the functional differences of the uterus that lead to successful implantation. Later, with decidualization, the binding proteins appeared first on the antimesometrial side, suggesting that the actual step of implantation also involves the retinoic acid signal.

In summary, we suggest that the spatial and temporal cell-specific expression of the retinoid-binding proteins during the periimplantation period relates to their roles in controlling retinoic acid production and its availability to the nuclear receptors in certain cells. However, the factors that produce this pattern are not known. In the prepubertal rat uterus and adult rat cervix, expression of the CRABPs and CRBP was found to be dynamically regulated by the steroid hormone estrogen. It has been reported that retinoic acid decreases both progesterone and estrogen receptor-mediated transcriptional activation and that retinoic acid can inhibit estrogen-induced uterine stroma and myometrial cell proliferation in vivo.
Moreover, retinoic acid can either induce or repress expression of several members of the transforming growth factor (3 superfamily in various cell lines and alter the expression of fibroblast growth factor family members. These polypeptide hormones are expressed in the uterus, and consequently the varying synthesis of retinoic acid suggested by this study may indicate that such interplay occurs during pregnancy. Clearly there are many factors and hormones participating in the maintenance of pregnancy. The expression pattern of retinoid-binding proteins defined here indicates that retinoic acid is one of those factors.